title: The Ktr potassium transport system in Staphylococcus aureus and its role in cell physiology, antimicrobial resistance and pathogenesis.
abstract: Potassium (K(+) ) plays a vital role in bacterial physiology, including regulation of cytoplasmic pH, turgor pressure and transmembrane electrical potential. Here, we examine the Staphylococcus aureus Ktr system uniquely comprised of two ion-conducting proteins (KtrB and KtrD) and only one regulator (KtrA). Growth of Ktr system mutants was severely inhibited under K(+) limitation, yet detectable after an extended lag phase, indicating the presence of a secondary K(+) transporter. Disruption of both ktrA and the Kdp-ATPase system, important for K(+) uptake in other organisms, eliminated regrowth in 0.1 mM K(+) , demonstrating a compensatory role for Kdp to the Ktr system. Consistent with K(+) transport mutations, S. aureus devoid of the Ktr system became sensitive to hyperosmotic conditions, exhibited a hyperpolarized plasma membrane, and increased susceptibility to aminoglycoside antibiotics and cationic antimicrobials. In contrast to other organisms, the S. aureus Ktr system was shown to be important for low-K(+) growth under alkaline conditions, but played only a minor role in neutral and acidic conditions. In a mouse competitive index model of bacteraemia, the ktrA mutant was significantly outcompeted by the parental strain. Combined, these results demonstrate a primary mechanism of K(+) uptake in S. aureus and a role for this system in pathogenesis.
authors.affiliation: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
authors.forename: Casey M
authors.initials: CM
authors.lastname: Gries
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Bose
authors.forename: Austin S
authors.initials: AS
authors.lastname: Nuxoll
authors.forename: Paul D
authors.initials: PD
authors.lastname: Fey
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Bayles
mesh_terms: D000617:Aminoglycosides / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D016470:Bacteremia / Q000382:microbiology / Q000473:pathology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D017353:Gene Deletion; D051379:Mice; D011188:Potassium / Q000378:metabolism*; D013203:Staphylococcal Infections / Q000382:microbiology / Q000473:pathology; D013211:Staphylococcus aureus / Q000235:genetics / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; D027682:Cation Transport Proteins; D014157:Transcription Factors; D037521:Virulence Factors; D011188:Potassium